The aim of this explore is to study the anti-inflammatory effect of Corilagin in herpes simplex virus (HSV)-1 infected microglial cells and HSV-1 infected mouse brain. The cellular model was set with microglial cells stimulated by HSV-1 and divided respectively, into virus, astragalus polysaccharides (APS), Dexamethasone and Corilagin group. A normal control group consisting of uninfected microglial cells was also included. ELISA for measuring TNF-alpha, IL-1beta and IL-10 and Greiss method for detecting NO secretion in supernatant, flow cytometry assay for examining apoptosis rate, expression of caspase-3, caspase-8, caspase-9 and caspase-12, and western-blot for measuring protein expression of cytochrome c were performed. The animal model was set up using Balb/c male mice that were intracranially inoculated with HSV-1. Animals were then divided in groups as described for the cellular model. Here, too a normal control group was included. HE staining was used to assay pathological changes in brain. As results, after Corilagin intervention, the release of TNF-alpha, IL-1beta and NO from HSV-stimulated migroglia cells was significantly inhibited. Furthermore, Corilagin induced apoptosis of HSV-stimulated microglia through all the 3 known apoptotic pathways. The animal model treated with Corilagin also displayed significant decrease of herpes simplex encephalitis induced brain pathological changes. In conclusion, Corilagin has the potential to reduce HSV-1-induced inflammatory insult to the brain, and its mode of action is through the induction of apoptosis of microglias and reduction of cytokines production.